tbuckley/cabot-search huggingface dataset:
The role of adjuvant chemotherapy (CT) for early stage resectable node negative small cell lung cancer with size of ≤ 2 cm post-surgical resection: A SEER plus based statistical analysis.
Authors: Pravash Budhathoki, Anish Kumar Shah, Suman Gaire, Lakshmi Bhavani Potluri, Dipesh Uprety
Journal: Journal of Clinical Oncology (2023)

e20643 Background: Small cell lung cancer (SCLC) is a poorly differentiated neuroendocrine tumor accounting for 15% of all lung cancers. Surgical resection followed by adjuvant platinum-etoposide is recommended for patients with limited-stage SCLC (T1 N0M0). In this study, we sought to evaluate the survival benefit of adjuvant chemotherapy for patients with ≤2 cm size SCLC following surgical resection. Methods: We utilized Surveillance, Epidemiology and End Results (SEER) plus 18 registries to identify adult patients (≥18 years) diagnosed with small cell cancer of the lung with tumor size of ≤ 2 cm from 2010 to 2018. The study population comprised of patients who underwent surgical resection followed by adjuvant chemotherapy and patients who received surgical resection alone. Kaplan-Meier and long rank tests were used to compare overall survival between the two groups. Multivariate survival analysis was done using the Cox proportional hazards regression model. Results: 419 patients were identified, with 203 (48%) receiving adjuvant CT while 216 (52%) not receiving adjuvant CT. The population who received adjuvant chemotherapy was younger than those who did not (Median years: 67 years vs 71 years, p &lt; 0.001). The 5-year overall survival rate was significantly higher for those receiving adjuvant CT (49% vs 40.9%, P value &lt; 0.001). On multivariate analysis after adjusting for age, gender, race, and origin, adjuvant chemotherapy was associated with better overall survival (HR:0.67; 95% CI 0.54 - 0.88, p = 0.003). Conclusions: Our study demonstrates that adjuvant CT should be used for early-stage small cell lung cancer irrespective of tumor size following surgical resection.
Phase 1/2 study of ARTS-021, a potent, oral administrated, selective CDK2 inhibitor, in advanced or metastatic solid tumors.
Authors: Yan Wang
Journal: Journal of Clinical Oncology (2023)

e17546 Background: ARTS-021 is an investigational, reversible, orally available CDK2 selective inhibitor that inhibits CDK2 at nanomolar potency and with over 600-fold selectivity against CDK1 (Liang J et al. AACR 2022). ARTS-021 has shown promising preclinical data, including strong single agent antitumor activity in CCNE1 amplified patient derived xenografts (PDX). Furthermore, consistent with the hypothesis that CDK2 activity may mediate resistance to CDK4/6 inhibitors, ARTS-021 significantly enhanced Palbociclib anti-tumor activity in an estrogen positive (ER+) breast cancer xenograft model. Taken together, these data support the clinical development of ARTS-021 as a monotherapy in CCNE1-amplified cancers and in combination with CDK4/6 inhibitors in ER+ breast cancer. Methods: A first in human, open label, multicenter phase1/2 dose escalation and dose expansion study will be conducted to evaluate the safety, tolerability, PK, pharmacodynamics (PD), and anti-tumor activity of ARTS-021 1) as a single agent in advanced or metastatic solid tumors harboring CCNE-1 gene amplification; 2) in combination with carboplatin to treat refractory/resistant CCNE-1 amplified ovarian cancer that has failed standard therapies; 3) in combination with endocrine therapy and CDK4/6 inhibitor to treat ER+/HER2- breast cancer patients have failed standard therapies. The phase 1 (dose-escalation) portion of the trial will have an accelerated dose escalation followed by a Bayesian Optimal Interval (BOIN) design. After the monotherapy recommended phase 2 dose (R2PD) is identified, the combination arms will be initiated at one dose level below the monotherapy R2PD. Phase1 primary endpoints are assessment of safety, tolerability, and pharmacokinetics (PK). The secondary endpoint is preliminary efficacy. Once the RP2D is defined for both monotherapy and in combination, the trial will be advanced into three Phase 2 expansion cohorts: monotherapy cohort (basket cohort), combination with carboplatin (ovarian cohort), and combination with endocrine therapy + CDK4/6 inhibitor (ER+ breast cancer cohort). The phase 2 primary end point is to estimate the anti-tumor efficacy in CCNE1 amplified cancer patients or CDK4/6 inhibitor resistant breast cancer patients. Objective tumor response rate will be measured per RECIST v1.1. The secondary endpoint of Phase 2 study will be safety/tolerability. Archival tumor and paired fresh tumor biopsy will be collected throughout the study for exploratory pharmacodynamics (PD) and biomarker evaluation. Results: ARTS-021 clinical study is ongoing. Conclusions: ARTS-021 shows potential anti-tumor activities.
Assessing the discordance rate of HER2 expression by immunohistochemistry between primary and secondary prostate cancer biopsies.
Authors: Joshua Mabellos, Puneet Gill, Coen Johannes Gerardus Lap, Alexandra Zara Rozalen, Guoqing Diao, Shanshan Liu, Shrina Thomas, Ramesh Subrahmanyam, Victor Nava, Maneesh Rajiv Jain
Journal: Journal of Clinical Oncology (2023)

e17014 Background: Preliminary evidence suggests that human epidermal growth factor receptor 2 (HER2) expression may play a role in tumor cell proliferation in prostate cancer. Minner et al ( Clin Cancer Res, 2010) identified a prevalence of ~ 20% HER2 expression in prostate cancer. The aim of the study is to assess the prevalence and discordance rate of HER2 expression in prostate cancer patients with multiple prostate biopsies using immunohistochemistry (IHC) at a Veterans Affairs hospital. Methods: A single-center, retrospective chart review of at least 30 patients with prostate cancer that had two prostate biopsies based on data collected from the Computerized Patient Record System (CPRS) and Veterans Information Systems and Technology Architecture (VISTA). Demographic and laboratory data including age, race, Gleason score, and stage of cancer were collected under IRB-approved waivers for consent and HIPAA authorization. Formalin-fixed paraffin embedded (FFPE) prostate tumors were evaluated for IHC analysis by the Washington DC Pathology Department. HER2 expression was assessed using the VENTANA anti-HER2/neu (4B5) rabbit monoclonal primary antibody and scored as 0, 1+, 2+, and 3+. HER2 scores of 0 and 1+ to 3+ were categorized as HER2-negative and HER2-positive, respectively. The primary endpoints are the prevalence and discordance rate of HER2 expression in paired prostate samples. Results: In our predominately African American (94%) cohort of 32 patients with a mean age of 60 years, overall HER2 prevalence was 25% (n = 8) and 56% (n = 18) in the primary and secondary biopsies, respectively. The mean time between biopsies was 41 weeks and overall HER2 discordance was 56% (n = 18). Discordance from HER2-negative to HER2-positive was 38% (n = 12), while discordance from HER2-positive to HER2-negative was 6% (n = 2). The remaining discordance were from HER2-low to HER2-positive or vice-versa. The most common variance between primary and secondary biopsies was observed as +1 HER2 scoring category (n = 11). No significant associations were found between HER2 discordance and Gleason score or stage of cancer . Conclusions: In our cohort of patients with prostate cancer, HER2 expression was observed in 25% of initial biopsies and over 50% of secondary biopsies. Discordance of HER2 expression was found in over 50% of patients. A few patients had initial HER2-positive biopsies and subsequent HER2-negative biopsies. The majority of HER2 discordance involved patients who had initial HER2-negative biopsies and secondary HER2-positive biopsies with most showing +1 difference in IHC scores. This study could lead to the consideration of utilizing multiple prostate cancer biopsies to determine the eligibility for anti-HER2 therapy in future trials.
Integrated clinico-genomic characterization of pancreatic ductal adenocarcinoma in an Asian population.
Authors: Kwangrok Jung, Jae Hyup Jung, Jinwoo Ahn, Bomi Kim, Jong-Chan Lee, Jaihwan Kim, Jin-Hyeok Hwang
Journal: Journal of Clinical Oncology (2023)

e16291 Background: Pancreatic cancer is a devastating malignancy with an extremely poor prognosis. However, the clinico-genomic understanding of pancreatic cancer that could play an important role to improve prognosis is highly limited, especially in Asian population. Methods: Using blood sample and primary pancreas tissues by endoscopic ultrasound guided fine needle biopsy (EUS-FNB) from 237 patients diagnosed with pancreatic ductal adenocarcinoma (PDA) at Seoul National University Bundang Hospital, WES and WTS were performed. Integrated clinico-genomic analysis was conducted by combining genomic data with diverse clinical information. Results: WES and WTS data were obtained from 205 and 93 patients, respectively. In WES, recurrent somatic mutations were identified in KRAS (89.3%), TP53 (68.8%), SMAD4 (22.4%) and CDKN2A (20.5%), and the overall mutation profile was not significantly different from TCGA dataset. Germline mutations related with hereditary cancer syndrome were found in 19 (9.3%), and BRCA2 mutation was the most common as in the Western data. At least one actionable mutation was reported in 61 (29.8%), and KRAS p.G12C, the emerging actionable mutation, was found in five (2.4%). In mutational signature analysis with single-base substitution (SBS), SBS1, SBS3 and SBS13 were identified in this cohort, and SBS3, a potential biomarker for DDR pathway related therapy, was positive in 25 (12.2%). Since this cohort contained 112 stage I-III (47.3%) and 125 stage IV (52.7%), genetic features according to stage or metastatic patterns were analyzed. There was no difference of mutation frequency and burden according to stage. However, liver metastasis was associated with higher frequency of TP 53 mutation (OR = 3.40; P = 0.010) and mutation burden was significantly lower in the lung metastasis (35.4 vs 50.9; P = 0.023). In the gene-set enrichment analysis using WTS, distinct pathways were observed according to the potential mechanism related with each metastatic pattern. Conclusions: Integrative clinico-genomic analysis of Asian PDA cohort provided various clues to better understand the genomic landscape of PDA.
Platinum/taxane/pembrolizumab vs platinum/5FU/pembrolizumab in patients with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC).
Authors: Lova Sun, Roger B. Cohen, A. Dimitrios Dimitrios Colevas
Journal: Journal of Clinical Oncology (2023)

6039 Background: Pembrolizumab +/- chemotherapy is standard of care for patients (pts) with r/m HNSCC. Despite approval of platinum/5FU/pembrolizumab based upon the KN-048 study, a taxane is often substituted for 5FU due to ease of administration and tolerability. No studies have directly compared these approaches. We describe nationwide patterns of taxane vs 5FU chemoimmunotherapy in r/m HNSCC and compare survival and time on treatment between the two. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database, and included pts treated with frontline pembrolizumab plus platinum-based chemotherapy (either taxane or 5FU) for r/m HNSCC. Demographic, cancer, and clinical outcomes were summarized. Categorical variables were compared using Pearson’s chi-square test; continuous variables were compared using T-test. Overall survival (OS) was estimated using Kaplan Meier methodology, and compared using log-rank test. Multivariable Cox regression for overall survival adjusting for age, sex, race, year of diagnosis, ECOG performance status (PS), smoking history, primary tumor site, PD-L1, HPV status, cisplatin use, socioeconomic status, insurance, and practice type was performed, with multiple imputation by chained equations for missing variables. Results: Of 444 pts, 321 (72%) received 5FU and 123 (28%) received taxane (108 paclitaxel, 15 docetaxel). Use of cisplatin rather than carboplatin was higher in the 5FU group than the taxane group (16.8% vs 4.9%, p=0.001). Taxane use was higher in academic vs community practices (50.7% vs 23.9%, p&lt;0.001); within community sites, Northeast states had highest taxane use (27.5%) and Western states had lowest taxane use (16.7%). Pts with Medicare or Medicaid were more likely to receive taxane (35.5%) vs commercial (23.6%) or other (26.7%) insurance. OS did not differ between taxane and 5FU groups (mOS 12.7 vs 13.5 months, p=0.743). On multivariable Cox regression, HR for death associated with taxane vs 5FU was 1.01 (95%CI 0.73-1.41). HPV positive status was associated with improved survival (HR 0.58, 95%CI 0.40-0.83). PS&gt;1 (HR 1.38, 95%CI 0.96-1.98) and cisplatin use (HR 1.37, 95%CI 0.95-1.98) showed non-significant trends towards worse survival. Taxane-treated pts received more treatment cycles (mean 11.3 vs 8.8 cycles, p=0.015) and were on treatment slightly longer (mean 6.9 vs 6.0 months, p=0.289) than 5FU-treated pts. Conclusions: In US pts with r/m HNSCC undergoing chemoimmunotherapy, rates of taxane vs 5FU use vary by academic setting, geographic region, and insurance status. There was no difference in survival between 5FU and taxane, and taxane-treated pts received more cycles of therapy. Platinum-taxane appears to be a non-inferior alternative to platinum-5FU with pembrolizumab for r/m HNSCC, and should be allowed in clinical trials.
Real-world analysis of commercially insured and Medicare Advantage patients with advanced cancer and rates of molecular testing.
Authors: Stacey DaCosta Byfield, Bela Bapat, Laura Becker, Brock Schroeder, Scott Spencer, Ismini Chatzitheofilou, Damon Hostin, John Leonard Fox
Journal: Journal of Clinical Oncology (2023)

6633 Background: Guideline-recommended molecular testing has become essential for biomarker-guided clinical decision making, particularly for patients with advanced (adv) disease. Several biomarkers have indications that are tumor type-agnostic (starting with MSI in 2017, NTRK in 2018, TMB in 2020, and RET and BRAF in 2022). Biomarker testing is covered by insurers, both Medicare (covers comprehensive genomic profiling [CGP] and non-CGP panels) and commercial (at least non-CGP). This study aimed to understand utilization of biomarker testing across tumor types. Methods: This retrospective analysis used de-identified administrative claims from Optum Labs Data Warehouse. Adult Commercial (COM) and Medicare Advantage (MA) enrollees diagnosed with any 1 of 6 adv cancer types from 1/2018 to 8/2021 were identified; the date of the first claim indicating adv cancer was the index date. Continuous enrollment for 12 months prior to (baseline), and ≥6 months post-index date, unless they died (follow-up) was required. Biomarker testing was captured using Current Procedural Terminology (CPT) codes indicating CGP (&gt; 50 gene panels), non-CGP (at most 5-50 gene panels), or CPT code 81479 (unlisted molecular pathology procedure) during the study period. The primary analysis evaluates testing in the follow-up only, with secondary analyses evaluating testing including the baseline (to account for testing prior to the index date). Results: We identified 16,931 breast (BC), 16,838 non-small cell lung (NSCLC), 8,755 colorectal (CRC), 4,244 pancreatic (PC), 2,610 ovarian (OC), and 1,231 gastric (GC) adv cancer patients meeting study criteria. Overall biomarker testing rates in the follow-up period were: 37% NSCLC, 19% BC, 41% CRC, 35% PC, 51% OC, 35% GC. The Table shows testing rates by cancer, insurance type, and panel size during follow-up. Testing rates were lower among MA patients compared to COM patients. Even considering baseline and follow-up periods, overall biomarker testing rates were low, and lower among MA compared to COM : 48% NSCLC (53% COM, 47% MA), 27% BC (34% COM, 22% BC), 56% OC (61% COM, 53% MA),42% PC (53% COM, 38% MA), 47% CRC (56% COM, 42% MA), 41% GC (54% COM, 35% MA). Conclusions: Considering guideline recommendations, rates of biomarker testing across tumor types are far from optimal despite insurance coverage for testing. Identification of barriers to biomarker testing and interventions to overcome these are needed to improve adherence to biomarker testing guidelines. [Table: see text]
Thyroid carcinoma showing thymus-like element: A national analysis of demographic features.
Authors: Gabriel Anthony Bitar, Beau Hsia, Xinxin Wu, Peter T. Silberstein, Darby Keirns
Journal: Journal of Clinical Oncology (2023)

e18099 Background: CASTLE, or Thyroid Carcinoma Showing Thymus-Like Elements, is an indolent and uncommon cancer that is believed to originate from either ectopic thymus tissue or remnants from the branchial pouches and affects the thyroid gland. It makes up a small portion, less than 0.1 - 0.15%, of all thyroid carcinomas and tends to affect slightly more females than males. Due to the lack of literature on this malignancy, understanding the trend in its diagnoses can provide valuable information about its epidemiology. The demographic factors of patients diagnosed with CASTLE were analyzed using data from the National Cancer Database (NCDB). Methods: A study was conducted using the NCDB from 2004 – 2020 to examine patients diagnosed with CASTLE (N = 23). Demographic factors such as age, sex, race, Hispanic ethnicity, education level, insurance coverage, type of medical facility, distance from the facility, and Charleson-Deyo score were analyzed using descriptive statistics. Trends in the incidence of the disease were analyzed through regression analysis. Results: The National Cancer Database was analyzed and revealed that 23 patients were diagnosed with CASTLE between the years 2004 to 2020, with a stable incidence rate per year (R2 = 0.1). The average age of diagnosis was 61.0 years (SD = 14.3, range = 31 – 87). The average Charlson-Deyo comorbidity score was 0.5, with 0 being the most common score (69.6%). The majority of patients (87.0%) were non-Hispanic and White. Most patients were found to be in the top two income quartiles (60.8%) earning more than $57,857 per year. A larger portion of patients had private insurance coverage (60.9%) compared to those who were uninsured or covered by Medicare/Medicaid. A greater number of patients lived in metropolitan counties with a population over 1 million (47.8%) than in other metropolitan counties (43.5%). Patients were more likely to receive treatment in a non-academic program (63.6%) such as community cancer programs, comprehensive community cancer programs, or integrated network cancer programs. On average, patients lived 11.4 miles (SD = 11.1, range = 0.7 – 46.7) from the treatment facility. Conclusions: This is the first analysis of CASTLE in the National Cancer Database, filling a significant gap in knowledge on the subject, particularly regarding the socioeconomic characteristics of CASTLE patients. The average CASTLE patient is a 60-year-old White, non-Hispanic male. These patients are more likely to be upper-middle-class citizens, have private insurance, live in densely populated metropolitan areas, and receive treatment at comprehensive community cancer programs. Further investigation is necessary to explore the statistical correlation between demographic and socioeconomic variables and the diagnosis, treatment, and outcomes of CASTLE patients.
The evolution of treatment patterns in patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) and clinical outcomes: Results of a longitudinal observational cohort study in England.
Authors: Seyed Hamidreza Mahmoudpour, Craig Knott, Mairead Kearney, Emmanuelle Boutmy, Patrice Verpillat
Journal: Journal of Clinical Oncology (2023)

e16559 Background: Treatment (tx) guidelines for pts with la/mUC in England have evolved over the last decade following the approval of successive immune checkpoint inhibitors (ICIs). However, the impact of this evolution on routine clinical practice (RCP) remains unclear. We aimed to describe shifts in tx patterns and associated clinical outcomes in RCP in England. Methods: This retrospective cohort study included pts aged ≥18 years, with primary stage III/IV UC diagnosis (dx) between Jan 1, 2013 and Dec 31, 2020, in the National Cancer Registration Dataset with follow-up to May 31, 2022. Pts’ dx were stratified at Dec 31, 2017, to split the cohort into pre- and post-ICI eras. Lines of systemic therapy were derived via an algorithm using data from the Systemic Anti-Cancer Therapy dataset. Summary statistics and overall survival (OS) were calculated and compared using χ 2 and log-rank tests, respectively. The Kaplan-Meier method was used to estimate median OS from dx and from systemic tx initiation. Results: In the pre- and post-ICI groups, the majority of pts were male (65.7% and 65.5%) and mean modified Charlson-Deyo Comorbidity Index was 3.4 and 3.5, respectively. Mean age was 73.2 years in both groups, while a higher percentage of pts in pre-ICI era had stage IV disease at dx (68.3% and 50.0%; p&lt;0.001). The rate of first line (1L) tx increased from 30.4% to 35.3% (p&lt;0.001) and second line (2L) from 31.2% to 37.3% (p&lt;0.001). The proportion of pts who received ICI in any line increased from 13.7% to 31.6% (p&lt;0.001). Median OS from 1L tx improved from 13.8 to 15.5 mo. Conclusions: While pt demographics did not change considerably between the two groups, 1L and 2L tx rates moderately increased over time, although remained below 40%. In both groups, &gt;85% of treated pts received 1L platinum chemotherapy, consistent with guidelines. In the post-ICI era, approximately one-third of treated pts received ICI therapy in any line. Improved OS from 1L tx could be partially attributable to the increased availability and uptake of ICIs. [Table: see text]